Organocatalysis is becoming an interesting area as it avoids the use of expensive and toxic metals. Ammonium triflate is a novel
organocatalyst which has been applied in a variety of reactions and displayed great catalytic activity and efficiency [12]. Furthermore,
ammonium triflate has many advantages, including easy separation, good reusability and environmental acceptability compared to
traditional Lewis acid catalysts. In connection with our continuing studies on the development of one-pot multicomponent reactions
catalyzed by ammonium triflates, we synthesized benzoxanthenes catalyzed by proline triflate (ProT) [12a] and 1,4-dihydropyridines
catalyzed by diphenylammonium triflate (DPAT) [12b]. We also investigated some other reactions catalyzed by DPAT [12c] or ProT
[12d]. Herein, we report an efficient and environmentally friendly method for the synthesis of dihydropyrano[2,3-c]pyrazoles catalyzed
by MorT.
2. Experimental
Analytical grade solvents and commercially available reagents were used without further purification. Melting points were
determined on a Büchi B-540 capillary melting point apparatus and uncorrected. All 1H NMR and 13C NMR spectra were recorded on a
VARAIN-400 using DMSO-d6 as the solvent with tetramethylsilane (TMS) as an internal standard. Chemical shifts are given in δ
relative to TMS; the coupling constants J are given in Hz. Mass spectra were measured with a Thermo Finnigan LC Advantage
(Agilent 1100). High resolution mass spectrometry (HRMS) was performed on an Agilent 6210 TOF LC/MS using ESI or EI
(electrospray ionization) techniques.
General procedure for synthesis of dihydropyrano[2,3-c]pyrazoles (5) (Scheme 1): To a pre-stirred mixture of ethyl acetoacetate (1)
(0.26 mL, 2.0 mmol), hydrazine hydrate (2) (0.13 mL, 2.5 mmol) in EtOH/H2O (v/v = 9:1, 6 mL) was added aldehydes (3) (2.0 mmol)
and malononitrile (4) (0.13 g, 2.0 mmol) followed by MorT (10 mol%). The resulting mixture was stirred under reflux. After
completion of the reaction (monitored by TLC, n-hexane/ethyl acetate = 3:1), the precipitated product was filtered and washed with
aqueous ethanol (10 mL). The crude residue was crystallized from ethanol/water (v/v = 9.5:0.5). 1H NMR and 13C NMR spectra for all
compounds are available in Supporting information.
NH2NH2
2a
CN
O
O
catalyst
CN
+
EtOH-H2O, reflux
CN
N
C6H5CHO
EtO
N
O
NH2
3a
1
4
H
5a
Scheme 1. General procedure for synthesis of dihydropyrano[2,3-c]pyrazoles.
Typical spectral data of some compounds are listed below, others are deposited in Supporting information.
6-Amino-3-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5a): Mp: 247-248 oC. 1H NMR (DMSO-d6, 400 MHz):
δ 12.07 (s, 1H), 7.32-7.28 (m, 2H), 7.22-7.19 (m, 1H), 7.15 (d, 2H, J = 7.2 Hz), 6.86 (s, 2H), 4.58 (s, 1H), 1.77 (s, 3H); 13C NMR
(DMSO-d6, 100 MHz): δ 160.5, 154.4, 144.1, 135.2, 128.1, 128.1, 127.2, 127.2, 126.4, 120.5, 97.4, 57.2, 36.2, 9.7; MS (ESI): m/z
251.3 [M-H]-.
o
1
6-Amino-4-(4-fluorophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5b): Mp: 223-224 C. H NMR (DMSO-d6,
400 MHz): δ 12.09 (s, 1H), 7.21-7.17 (m, 2H), 7.12 (t, 2H, J = 8.8 Hz), 6.89 (s, 2H), 4.62 (s, 1H), 1.78 (s, 3H); 13C NMR (DMSO-d6,
100 MHz): δ 161.8, 160.5, 159.4, 154.4, 140.4, 135.3, 129.0, 120.4, 115.0, 114.8, 97.3, 57.1, 35.4, 9.7; MS (ESI): m/z 269.3 [M-H]-.
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1
6-Amino-3-methyl-4-(p-tolyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5j): Mp: 208-209 C. H NMR (DMSO-d6, 400
MHz): δ 12.05 (s, 1H), 7.10 (d, 2H, J = 8.0 Hz), 7.03 (d, 2H, J = 8.0 Hz), 6.82 (s, 2H), 4.53 (s, 1H), 2.26 (s, 1H), 1.78 (s, 3H); 13C
NMR (DMSO-d6, 100 MHz): δ 160.4, 154.5, 141.2, 135.4, 135.3, 128.7, 128.7, 127.1, 127.1, 120.6, 97.6, 57.4, 35.9, 20.7, 9.8; MS
(ESI): m/z 265.3 [M-H]-.
o
1
6-Amino-3-methyl-4-(4-nitrophenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5n): Mp: 250-251 C. H NMR (DMSO-d6,
400 MHz): δ 12.17 (s, 1H), 8.19 (d, 2H, J = 8.8 Hz), 7.45 (d, 2H, J = 8.8 Hz), 7.04 (s, 2H), 4.82 (s, 1H), 1.80 (s, 3H); 13C NMR
(DMSO-d6, 100 MHz): δ 160.8, 154.4, 151.7, 146.1, 135.6, 128.6, 128.6, 123.6, 123.6, 120.2, 96.4, 55.9, 35.9, 9.8; MS (ESI): m/z
296.3 [M-H]-.
6-Amino-4-(2,4-dichlorophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5r): Mp: 220-221 oC. 1H NMR (DMSO-
d6, 400 MHz): δ 12.14 (s, 1H), 7.57 (d, 1H, J = 2.0 Hz), 7.39 (dd, 1H, J = 8.4 Hz), 7.20 (d, 1H, J = 8.0 Hz), 7.00 (s, 2H), 5.05 (s, 1H),
1.78 (s, 3H); 13C NMR (DMSO-d6, 100 MHz): δ 161.0, 154.6, 139.8, 135.2, 132.6, 131.9, 131.9, 128.6, 127.8, 120.0, 96.2, 55.3, 33.1,
9.4; MS (ESI): m/z 319.2 [M-H]-.
6-Amino-4-(3,4-dimethylphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5s): Mp: 201-202 oC. 1H NMR
(DMSO-d6, 400 MHz): δ 12.02 (s, 1H), 7.04 (d, 1H, J = 7.6 Hz), 6.88-6.85 (m, 2H), 6.80 (s, 2H), 4.48 (s, 1H), 2.17 (s, 6H), 1.78 (s,
3H); 13C NMR (DMSO-d6, 100 MHz): δ 160.4, 154.4, 141.6, 135.8, 135.3, 134.2, 129.2, 128.2, 124.7, 120.6, 97.6, 57.5, 35.9, 19.5,
19.0, 9.8; MS (ESI): m/z 303.5 [M+Na]+. HRMS (ESI+ , m/z): [M+H]+, calcd. for C16H17N4O: 281.1397, found: 281.1399.
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6-Amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5aa): Mp: 168-169 C. H NMR (DMSO-d6, 400
MHz): δ 7.78 (d, 2H, J = 7.6 Hz), 7.50-7.46 (m, 2H), 7.34-7.26 (m, 3H), 7.26-7.24 (m, 3H), 7.22 (s, 2H), 4.67 (s, 1H), 1.78 (s, 3H); 13C
NMR (DMSO-d6, 100 MHz): δ 159.1, 144.9, 143.6, 143.3, 137.3, 129.0, 129.0, 128.2, 128.2, 127.5, 127.5, 126.7, 125.8, 119.7, 119.7,
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